Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

All Conditions

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Neoplasms

Digestive System Diseases

Mouth and Tooth Diseases

Asthma

Nasal Polyps

Colorectal Neoplasms

Nasopharyngeal Neoplasms

Polyps

Bronchial Diseases

Respiratory Tract Diseases

Lung Diseases

Lung Diseases, Obstructive

Hypersensitivity

Respiratory Hypersensitivity

Hypersensitivity, Immediate

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Nose Diseases

Pathological Conditions, Anatomical

All Drugs and Chemicals

Anti-Allergic Agents

Respiratory System Agents

Antibodies

Antibodies, Monoclonal

Omalizumab

Immunoglobulins

Anti-Asthmatic Agents

Omalizumab (Xolair(R)) is a recombinant DNA-derived humanized IgG1 monoclonal antibody that selectively binds to human IgE. Molecular weight is approximately 149 kilodaltons. Xolair(R) is a sterile, white, preservative-free, lyophilized powder contained in a single-use vial, reconstituted with Sterile Water For Injection (SWFI), and administered as subcutaneous (SC) injection.

Xolair(R) will be administered subcutaneously in a dose of 75 to 375mg every 2 to 4 weeks. Doses (mg) and dosing frequency are determined by total serum IgE level (IU/ml) measured at the start of treatment and body weight (kg). During this 20-week during trial patients will receive 4 or 8 doses of omalizumab.

Placebo

Paul Van Cauwenberge, PhD, MD

This pilot study is a double-blinded, randomized controlled, two-centre trial in which subjects will receive 4 to 8 (subcutaneous administered) doses of medication (Omalizumab or placebo) (dose and dosing interval calculated on body weight and baseline total serum IgE). During the treatment period and follow-up, the clinical efficacy of the treatment will be assessed by evaluation of symptoms, Quality of Life questionnaire, morning Peak Expiratory Flow measurement, smell test, nasal endoscopy, CT-scan, peak nasal inspiratory flow and spirometry. Biological activity will be evaluated by measuring peripheral and local (in serum, in nasal secretions, biopsies) markers of inflammation.

Study hypothesis

1. Evaluation of the efficacy and safety of anti-IgE (Omalizumab) in patients with nasal polyposis and comorbid asthma.
2. Exploration of anti-IgE effects on local and systemic metabolism of IgE in nasal polyposis
3. Clinical assessment of the IgE theory in the pathogenesis of nasal polyps

Clinical and Biological Effects of Anti-IgE (Omalizumab) in Patients With Bilateral Nasal Polyposis and Asthma

Nasal examination at all visits by endoscopy of each nasal fossa. Polyps will be graded by the Modified DAVOS score

Novartis Pharma AG, Switzerland

University Hospital, Ghent

Prof. Dr. P. van Cauwenberge

25 mg AK001 will be administered as multiple doses

250 mg AK001 will be administered as multiple doses

A placebo comparator consisting of inactive excipients will be administered as multiple doses

AK001 low dose

AK001 high dose

Placebo will be administered as multiple doses

Claus Bachert

This is a phase 2 study to evaluate multiple doses of AK001 across 2 active doses. Pharmacodynamic activity will also be evaluated.

AK001 is a monoclonal antibody which may be useful in the treatment of patients with moderate to severe nasal polyposis

Study to Evaluate Multiple Doses in Patients With Nasal Polyposis

A Phase 2, Randomized, Double-blind, Placebo-controlled, Study to Evaluate Multiple Doses of AK001 in Patients With Moderate to Severe Nasal Polyposis

NPS was the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Change in TPS from Baseline (prior to the first dose) to Week 12 (Day 84) was the primary outcome of the study. TPS ranges from 0 to 8 (scored 0 \[no polyp\] to 4 \[large polyps\] for each nostril), with a lower score indicating smaller-sized polyps, a higher scores mean a worse outcome.

Allakos Inc.

If a patient completed the study with an ongoing adverse event (AE), investigational site personnel continued to follow-up until AE resolution and the documentation thereof. If, after 30 days from the study completion date, the AE was still continuing but not assessed as serious, the outcome was recorded as ongoing.

25 mg AK001 was administered as a single IV infusion through a peripheral vein on Days 0, 21, and 49.

25 mg AK001

250 mg AK001 was administered as a single IV infusion through a peripheral vein on Days 0, 21, and 49.

250 mg AK001

Placebo was administered as a single IV infusion through a peripheral vein on Days 0, 21, and 49.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Europe

Region of Enrollment

Total Polyp Score (TPS)

After 40 of the 70 patients planned were randomized in the study, enrollment was stopped as the Sponsor decided not to pursue further development of AK001. The study was not stopped for any safety concern. Early termination resulted uninterpretable data.

Henrik Rasmussen, MD, PhD, Chief Medical Officer

250 mg AK001 was administered as a single IV infusion through a peripheral vein on Days 0, 21, and 49

Modified Intent-to-Treat (MITT) population included all randomized subjects who have taken at least one dose of the study drug and had both a baseline and at least one post-baseline efficacy assessment.

Change in Total Polys Score (TPS)

Overall Study

Jean-François PAPON, PhD

Lise Crevier Buchman, PhD

Lise Crevier_Buchman, PhD

"Nasal polyposis is a chronic inflammation of the sinonasal mucosa which is characterized by the development of polyps in the sinonasal cavities. In the general population, its prevalence is 4% with a clear increase from the age of 50 years.

When drug treatment is not effective, and the patient's quality of life is impaired, surgery is proposed. It allows to widen the nasal cavities with aerodynamic and acoustics effects on speech. There are few studies, that have focused on the impact of NP and its treatment on speech. Yet there is a real demand from patients to obtain answers related to the impact of this surgery on their voice.

Preoperatively and postoperatively, the resonance will be disturbed: polyps will impacted the quality of the nasal sounds. And after surgery, the new anatomical shape can create an excessive resonance in the nasal cavities.

Indeed, there is a diversity of acoustic effects that differ according to the sinuses involved, the nature and type of surgery and the anatomical and physiological specificities of the patient.

The impairment of acoustic properties after surgery is diverse and little known.

The surgery improves the communication between sinuses and nasal cavities but the real impact on nasal resonance still unknown.

The particularity of this pathology stands in the obstruction of the sinonasal cavity by polyps. On this study, it represents a model of nasality disturbance/impairment ? Indeed, all aspects of nasality will be altered : the articulation by the obstruction of the sino-nasal cavities, the aerodynamic by a disturbance of the circulation of the airflow within the nasal cavity, acoustics by an alteration of the resonance of this flow, and finally the perception of speech by others where the comprehension of speech is difficult. Thus, the investigators wish to observe this dysfunction in a multipara metric way in order to have an accurate approach.

This population is therefore ideal. In preoperative, it will allow to measure by aerodynamic, articulatory, acoustic, and perceptive data taking this dysfunction, to give precise answers. Then, postoperatively, these measurements will be repeated to observe a return to the expected functioning of the nasal cavity. Indeed, the cavities being no longer congested, a greater flow of nasal air would be expected, which would have acoustic consequences on the resonance of nasal sounds. This could be accentuated because of the new anatomical configuration due to the surgery. Perceptually, the voice after surgery should no longer be considered as pathological.

In addition to the linguistics aspect, this population has the particularity of having a strongly impacted quality of life. The investigators would therefore like to measure this impact on quality of life before and after surgery.

For this study, the main objective is to measure the articulatory, aerodynamics, acoustics and perceptive impact of the nasal polyposis on speech before and after surgery.

the secondaries objectives are to:

* Compare the differences in aerodynamic, acoustic, articulatory and perceptual changes between the ""presence of polyps in the nasal and sinus cavities"" group and the ""presence of polyps in the sinus cavities"" group
* Compare the modifications on the speech of the pathology before and after surgical treatment
* Identify the elements related to the quality of life impacted by this pathology.
* Identify the glottic compensation strategies induced by the pathology
* Compare preoperative and postoperative nasal resonance and the relationship between nasal and sinus cavities using 3D models
* Validate the adequacy of the nasality-speech questionnaire for patients with sinonasal polyposis"

"Nasal polyposis, a pathology related to speech Nasal polyposis (NP) is a chronic bilateral inflammation of the sinonasal mucosa characterized by the development of polyps in the sinus and nasal cavities. In the general population, its prevalence is 4% with a clear increase from the age of 50 years. Two clinical forms of NP exist: primary polyposis which is isolated or integrated in Widal's disease, secondary polyposis when it appears in the context of diseases such as cystic fibrosis, ciliary dyskinesia or immune deficiencies. NP is a diffuse rhinosinusitis, i.e. it affects both the anterior and posterior sinuses bilaterally. When drug treatment is not effective, and the patient's quality of life is impaired, surgery is proposed.

Surgical treatment consists of removing the polypoid mucosa to repermeabilize the nasal cavities and/or to enlarge the ostia (communication openings between the nasal cavities and the sinuses) and to allow drainage again. This surgery goes beyond the repermeation of the sinuses since it will allow to widen the nasal cavity with aerodynamic and acoustic consequences on speech; indeed, it will allow to bring a greater resonance of the vocal and nasal duct. To our knowledge, there are few studies that have focused on the impact of NP and its treatment on speech. Yet there is a real demand from patients to obtain answers related to the impact of this surgery on their voice. A pathology such as NP falls directly within the scope of clinical phonetics, i.e. the description and understanding of the mechanisms of articulatory and acoustic production of speech, applied to the pathology. The NP will disturb the communication on the production side by altering the nasal resonance essential in the production for the distinction between oral and nasal sounds but also on the receiver's side who will have difficulties to understand the message.

Thus, preoperatively and postoperatively, the resonant capacities will be disturbed: in the sense of a hyponasality before surgery due to the presence of polyps which will affect the quality of nasal sounds. Then potentially, the risk of a hypernasality after surgery because of the new anatomical configuration. Indeed, there is a diversity of acoustic effects that differ according to the sinuses involved, the nature and type of surgery and the anatomical and physiological specificities of the patient. The alteration of acoustic properties of phonemes after endonasal sinus surgery is diverse and not well known. It is known that NP surgery allows better communication between the sinus and nasal cavities but the real impact on nasal resonances is not known. The same is true for the activity of the vocal folds. There is a link between nasality and voicing, i.e. the vibration of the vocal folds necessary for the production of voiced sounds. Nasality favors voicing. Indeed, to establish voicing, the maintenance of an airflow through the glottic plane is necessary, a passage of air through the nasal cavity facilitates the maintenance of this flow. Preoperatively, since air cannot pass through the nasal cavity, compensatory mechanisms may appear, such as increased voicing or glottic thrust. Thanks to electroglottography, the quality of this voicing preoperatively and postoperatively will be observed.

The NP can therefore be an obstacle to the phenomenon of nasality. Indeed, the airflow in the nasal cavities will be disturbed because of the presence of polyps, which will have consequences on the resonance of these cavities as a whole. This project would provide a deeper understanding of the mechanism of nasal production. It results from the coupling of two cavities: the nasal and oral cavities, which will produce an anti-resonance phenomenon (a resonance phenomenon specific to nasality) and make this resonance process extremely complex. The impact of nasality on the acoustic signal is known (anti-formants etc.) but these manifestations remain diverse and dependent on individual anatomical variability. The impact of the sinuses on speech remains poorly understood today. The controversy between researchers on their influence on speech, encourages us to better explore their role in speech. But also to analyze the phenomenon of resonance before and after surgery to understand the consequences on speech intelligibility and the predictability of the consequences on the speech of patients postoperatively.

Understanding dysfunction in the context of NP will allow us to learn more about the functioning and production mechanisms of nasality in general.

The articulatory approach is central to our project. The articulation of speech differs according to the nature of the sound: the production of consonants will require a closure or a constriction in the oral cavity while for vowels the free passage of air is necessary. In addition to the mode of articulation, the sounds are also characterized by the cavity that enters in resonance: only the oral cavity or in addition to this last the nasal cavity. The resonance of the air within the nasal cavity will therefore allow the production of nasal sounds. Thus, the volume of the sinonasal cavities and the relationship between the nasal cavity and the sinuses have a role in the articulation of these nasal sounds. Medical imaging is our means of studying their articulation since it will allow us to quantify and visualize the sinonasal cavities and their mutual relationship. It will allow us to precisely grasp the extent of the impact of the sinuses on speech. These scannographic data will be compared with aerodynamic, acoustic and perceptual data.

The particularity of this pathology lies in the obstruction of the nasal and sinuses cavities by polyps. In the context of our study, it represents a model of disturbance of the nasality. Indeed, all the aspects of the nasality will be altered: the articulatory by the obstruction of the cavities, the aerodynamics by a disturbance of the circulation of the air flow within the nasal cavity, the acoustics by an alteration of the resonance of this flow, the vibration of the vocal folds by phenomena of compensation, and finally the perception of speech by others where the comprehension of speech is difficult. Thus, this dysfunction should to be observed in a multiparametric way in order to have a precise approach.

This population is thus ideal, in preoperative, it will allow to measure by aerodynamic, articulatory, acoustic, and perceptive data taking this dysfunction and to give precise answers. Then, postoperatively, these measurements will be repeated to observe a return to the expected functioning of the nasal cavity. Indeed, the cavities being no longer congested, a greater nasal airflow would be expected, which would have acoustic consequences on the resonance of nasal sounds. This could be accentuated because of the new anatomical configuration due to the surgery. Perceptually, the voice after surgery should no longer be considered as pathological. And on the glottic level, the phenomena of compensation would no longer be present.

In addition to the linguistics aspect, this population has the particularity of having a strongly impacted quality of life. the investigators would therefore like to measure this impact on quality of life before and after surgery.

The research focuses on a voice recording: an aerodynamic recording with a mask and an acoustic recording with a microphone and an electroglottograph.

Finally, with the acoustic data, a perception test will be designed to observe whether naive listeners perceive this alteration of nasality.

This research also focuses on self-assessment questionnaires of quality of life:

These questionnaires allow to understand the image that the speaker has of his/her voice. In the context of patients, the difficulties that people with rhino-sinus pathologies may have in their daily life will be understood.

The participants will complete two voice-specific questionnaires: the Voice Handicap Index (VHI) and the Speech Handicap Index (SHI).

Finally, a questionnaire of 4 questions dealing more specifically with the phenomena of nasality will be proposed. But also on the adaptations put in place by the speaker to speak and on the difficulty to read the corpus. One part of the questionnaire comes from a study by Behrman \& al (2002) and the other one was made by investigators.

The multiparametric approach is necessary for phonetic studies and even more so in the case of nasality, which is a complex phenomenon whose manifestations are different depending on whether one is looking at it from the articulatory, aerodynamic or acoustic point of view.

The manifestations of nasality are different depending on whether one is looking at it from the articulatory, aerodynamic or acoustic point of view. In order to have an optimal understanding of nasality and its alterations in the context of NP, the observation cannot be limited to aerodynamic, acoustic, and perceptual parameters alone.

To date, no speech-related study has sought to quantify sinus volume. The use of scannographic data (low-dose CT) is already used by the ENT surgeon to visualize the extent of polyps in the sinuses preoperatively and to verify the effectiveness of the intervention. It is essential to this study in order to theorize the morphological variability of the sinuses: bilateral volume asymmetry. Knowing the variability of the sinuses will allow to estimate their impact on nasal resonance and eventually on voice and speech. Postoperatively, the CT scan will allow to quantify the anatomical changes related to the surgery.

Imaging data, with these two scans before and after surgery, will allow to quantify the volumes of the nasal cavities and sinuses, and to quantify the volume of the polyps, which will lead to a 3D reconstruction. The latter will lead to acoustic simulations. The quantification of the volumes coupled with a 3D reconstruction will thus be central to this project and will allow to deepen the knowledge and to target the relationship between the sinuses and the resonance, and the relationship between the sinuses and the phenomenon of nasality.

The study of the impact of NP and surgery on speech could therefore represent a major help for the clinician to provide answers to patients and inform them of possible changes. Indeed, at present, there are no models capable of predicting the possible acoustic and aerodynamic consequences of surgery.

This articulatory aspect is particularly innovative because currently, to knowledge, there are no correlations between the medical imaging data of the sinuses (volume, geometry of the sinonasal cavities...) and the production of speech.

Patients will be recruited from the active file of patients followed in the recruiting center according to the eligibility criteria. After verification of the inclusion and non-inclusion criteria, the investigator will propose to the patients to participate in the study and will deliver the information and collect their non-opposition.

Then, the patient will be included in the study and an information and non-opposition form for the research will be given to him.

Clinical and para-clinical data (CT scan and nasal endoscopy), demographic and socio-demographic data, medical history, sinus quality of life questionnaire (SNOT-22) performed as part of the care will be collected in the observation booklet. In addition, voice recordings and voice and nasal-specific quality of life questionnaires (VHI, SHI and nasal-speech relationship) will be made for the purpose of the research. These data will be collected during two visits of the patient's care (preoperative visit and 3 months postoperative visit). The voice recordings will take place during these two visits and will last approximately 20 minutes. They will take place in the same way preoperatively and postoperatively.

Preoperative visit: The voice recording and the quality of life questionnaires at the preoperative visit will take place either during the visit with the ENT surgeon where the non-opposition will be collected, or during the anesthesia consultation. This will be determined according to the patient's expected waiting time during these appointments.

Post-operatively, the recording will take place during the ENT check-up appointment scheduled in the care pathway.

The recording will take place as follows:

* A presentation of the recording equipment by the research team.
* The patient will place the mask on his face and the electroglottograph around his neck.

During the recording, the patient will be asked to read a text.

- Finally, the patient will fill in the 3 voice quality questionnaires. Once the patients are recorded, a data processing phase will follow: segmentation of the recordings, analysis and acoustic and aerodynamic measurements.

Included patients will be reviewed at their M3 postoperative follow-up appointment with the same data collection and examinations as the preoperative visit.

The clinical data related to the current care and the data of the questionnaires will be collected in real time or a posteriori by the investigators and/or by the doctoral student Amélie Elmerich on a paper support at first. The aerodynamic and acoustic data will be collected on the doctoral student's professional computer simultaneously with the reading of the text by the patient, using the acoustic and aerodynamic data acquisition software QuickDaq.

The data directly collected in the CRF will be the recording data: aerodynamic, acoustic, electroglottographic recording, and the scores obtained from the questionnaires (VHI, SHI, nasal-speech questionnaire).

Care-related data:

This is a non-interventional study. All clinical, socio-demographic (age, sex, languages spoken, professional status), para-clinical, medical history data, the practice of an activity that requires an important use of the voice (singing, theater, wind instruments, teaching...), the consultation of a professional for voice, language, speech problems will be collected during usual care. All these data will be collected in a pseudonymized way (patient reference in the study: center number - enrollment number in the center - initials) from the patient's medical record (source record).

Socio-demographic data, the practice of an activity that requires an important use of the voice (singing, theater, wind instruments, teaching...) and the consultation of a professional for voice, language, speech problems. These data, specific to the individual, will allow us to understand certain results, they can have an influence on the results. They will also allow us to make hypotheses about a result that would be below or above the average values (flow, value of formants...). But also to observe through certain parameters which would be common (sex, age, profession etc.) between participants if there are similarities in their aerodynamic or acoustic results.

Research-related data:

Research-specific quality of life questionnaires will be collected in the Case Report Form (CRF).

The recordings (aerodynamic and acoustic data) will be collected by the doctoral student Amélie Elmerich at the Bicêtre hospital simultaneously with the recording of the patient, when he will read the text on the QuickDaq software.

The data will then be analyzed by her at the Phonetics and Phonology Laboratory (Sorbonne Nouvelle University).

The collection of voice data (acoustic and aerodynamic recording, quality of life questionnaires) will take place at the Bicêtre hospital. Then these data will be transferred to the Université Sorbonne Nouvelle where they will be processed by the doctoral student Amélie Elmerich under the responsibility of Lise Crevier-Buchman and Angélique Amelot. The statistical analysis will be carried out by the doctoral student Amélie Elmerich.

As this study is observational, there is no statistical justification for the number of patients. This number of participants (30) is chosen because it allows to make sufficient subgroups in terms of location of polyps and stage of severity in order to perform a phonetic analysis later on.

Inferential and descriptive statistics will be performed. The descriptive statistics will allow a first approach, it will be a question of using descriptive statistics in order to obtain average values, standard deviations and the range of duration of the sounds, oral and nasal airflow.

Inferential statistics will allow to complete the descriptive approach thanks to hypothesis tests (Anova for example) and thanks to the creation of a linear mixed model. The analysis will be conducted within each group (""Presence of polyps in the nasal and sinus cavities"", ""Presence of polyps in the sinus cavities"") by comparing different parameters (aerodynamic, acoustic, articulatory and perceptual) in order to highlight significant changes between preoperative and postoperative.

Then, variables such as gender or severity stage will be used to measure their potential impact on statistical results.

A linear mixed model will be established to observe the effect of surgery, gender and stage of severity on aerodynamic (oral and nasal airflow), acoustic (formant measurements) and articulatory (sino-nasal cavity volume) measurements.

This study is based on a voice recording. In case of missing data in a recording, the rest of the data present will still be taken into account and analyzed"

Nasality Evolution in a Nasal Polyposis Context : Multiparametric Evaluation : Articulatory (Imaging), Aerodynamics, Acoustics and Perception

Nasality Evolution in a Nasal Polyposis Context: Multiparametric Evaluation: Articulatory (Imaging), Aerodynamics, Acoustics and Perception

For the aerodynamic measure : with a fibermask, we will record the nasal and oral airflow in liter/second

For the acoustic measure with a microphone, we will record data in Hertz.

To complete questionnaires : The nasal-speech relationship

Sorbonne University

Assistance Publique - Hôpitaux de Paris

Anti-Infective Agents

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Doxycycline

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Administration of oral methylprednisolone

Claus Bachert, MD, PhD

This study is a double-blinded, randomized, placebo controlled, multi-center trial in which 120 subjects with nasal polyposis (NP) will be treated during 20 days with oral corticosteroids (OCS) in decreasing doses or oral doxycyclin (ODOX) or placebo. At each visit the clinical and the biological activity will be assessed by nasal peak inspiratory flow (nPIF), symptoms, olfactory test, endoscopic evaluation of nasal polyps, peripheral eosinophil levels and markers of inflammation IL-5, IL-5 receptor alpha, ECP, TGFβ1, IgE and specific IgE in serum and nasal secretion.

Double-Blind Randomized Placebo-Controlled Trial on Clinical and Biological Effects of Oral Corticosteroids or Doxycyclin in Patients With Nasal Polyposis

Infections

Skin and Connective Tissue Diseases

Rare Diseases

Chronic Disease

Rhinitis

Rhinosinusitis

Ganglion Cysts

Synovial Cyst

Cysts

Communicable Diseases

Respiratory Tract Infections

Disease Attributes

Sinusitis

Paranasal Sinus Diseases

Mucinoses

Connective Tissue Diseases

Chronic Graft Versus Host Disease

Central Nervous System Depressants

Antirheumatic Agents

Analgesics

Vasoconstrictor Agents

Adjuvants, Anesthesia

Anticonvulsants

Muscle Relaxants, Central

Psychotropic Drugs

Vasodilator Agents

Anesthetics

Ibuprofen

Bupivacaine

Epinephrine

Botulinum Toxins

Botulinum Toxins, Type A

abobotulinumtoxinA

Diclofenac

Diazepam

Racepinephrine

Epinephryl borate

Acetylcholine

Cholinergic Agents

Neurotransmitter Agents

* Preoperative medication: Paracetamol 1,5g oral, diclofenac 50mg (evt ibuprofen 600mg) oral and/or diazepam 5-10 mg oral.
* Skin and tissue inside the projected injection canal will be infiltrated with 5-10ml Marcain-Adrenalin (5mg/ml + 5microg/ml) for local anaesthesia.
* Localization will be confirmed with help of navigation before the medication will be given. Intravascular injection will be prevented by control of aspiration.

botox injection under CT/MR navigation and with the navigation tool MultiGuide

botox injection Multiguide

Lars Jacob Stovner, md prof

Chronic rhinosinusitis (CRS) with nasal polyps is a particularly challenging form of chronic rhinosinusitis in several ways. Patients have significantly more severe symptom burden and worse quality of life than patients with chronic rhinosinusitis without nasal polyps. Many patients return to the health care providers with persistent symptoms after repeated medical and surgical treatment. Patients have usually tried several different types of treatments, ranging from less invasive procedures to extensive surgical treatment. The surgical treatment is often repeated several times. The most common surgical treatment is functional endoscopic sinus surgery, another established procedure is Vidian neurectomy.

The main object of this pilot study is to investigate the safety of onabotulinumtoxin A towards the sphenopalatine ganglion (SPG) in CRS patients with nasal polyps. Efficacy data will also be collected to provide indication on whether future placebo-controlled studies should be performed.

Onabotulinumtoxin A inhibits the secretion of acetylcholine, blocking the parasympathetic reflex cascade in the SPG. As a result, the investigators expect less mucosal swelling, secretion and nasal polyps. The duration of such a blockade is believed to last for 3-9 months and will not lead to damage of the nerve.

This study opens up for improved treatment with less complications.

Botulinum Toxin Type A Block of the Sphenopalatine Ganglion in Chronic Rhinosinusitis With Nasal Polyposis

Registration of all adverse events sorted by probable relation to botox or surgery. Data collected from symptom diary, in addition to an open question at consultation and put into the Case Report Form (CRF) by physician or nurse.

St. Olavs Hospital

Norwegian University of Science and Technology

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Mometasone Furoate

Methotrexate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

10 mg Emthexate, PO, once a week during 8 weeks

200 mcg/day, intranasal mometasone furoate, for 8 weeks

After randomization, the patients were divided into three groups including 14 volunteers in each study groups and 11 in the control group. One of the study groups was take methotrexate (n=14, eight weeks) and the other was take methylprednisolone (n=14, eight week)

Emthexate

Prednol

Yesim Tuncok, MD

Chronic rhinosinusitis with nasal polyposis (CRwNP) is an inflammatory disease of the nasal mucosa. It is presented with severe stuffiness, nasal discharge, facial pressure/pain, and sleep disorders. It leads to severe inconvenience to social life and the quality of life. The first step standard medical therapy consists of the topical intranasal or systemic corticosteroids. Surgery should be considered in the case of medical treatment failure. However, the recurrences are common after both surgery and medical therapies in severe disease and usually require revision surgeries or high dose corticosteroid regimens. On the contrary, either the revision surgeries or the high dose corticosteroid therapies are not capable of preventing the recurrences, treatment failures. Besides, revision surgeries usually lead to high complication rates and high dose corticosteroids usually cause severe adverse effects. The use of the short course topical intranasal corticosteroids after the surgery is generally advocated for these patients. However, the recurrence rates are still high. Hence a new and effective maintenance treatment algorithm with no severe adverse effects is required.

The hypothesis of the clinical trial is an estimated symptom recovery and superiority in both efficacy and safety by the use of low-dose methylprednisolone or methotrexate as compared to the standard maintenance therapy in treatment-resistant CRwNP patients. Therefore, the results of the present study are believed to provide data on novel maintenance therapy and suggest an alternative to the topical intranasal corticosteroids or the high-risk revision surgery.

Methotrexate, as an anti-inflammatory drug used in animal experiments, and low dose systemic corticosteroid treatments have recently been suggested for the treatment of the CRwNP. Despite the several case reports of methotrexate being used for the severe and treatment-resistant CRwNP, the literature is a lack of clinical trials. Likewise, low-dose corticosteroid regimens have not been tested well contrary to the high dose corticosteroid therapy in the same course of the disease. Therefore, the main purpose of this study is to compare a low-dose of methylprednisolone or a low dose of methotrexate treatments with the standard intranasal, topical corticosteroid treatment in human volunteers with medical and surgical treatment-resistant CRwNP.

The present study was planned as a randomized, controlled, triple armed, parallel, open-label phase 2 clinical trial which is conducted in the Department of Otorhinolaryngology at Dokuz Eylül University Hospital. Human volunteers with CRwNP who are resistant to the medical and surgical therapies were recruited to the study. After randomization, the patients were divided into three groups including 14 volunteers in each study groups and 13 in the control group. One of the study groups was take methotrexate (n=14, eight weeks) and the other was take methylprednisolone (n=14, eight weeks). Each patient were evaluated by endoscopic examination, the nasal air-flow, the smell threshold, and the blood biochemistry both before and after the medications.

Efficacy goals of the study are located at below:

1. Primary efficacy variable: Lund-Kennedy endoscopic grading system (NPS)
2. Secondary efficacy variables: Total visual analog scale (VAS) score; the Turkish version of the Sinonasal Outcome Test-22 (SNOT-22); sum score of the peak nasal inspiratory flow (PNIF) and butanol olfactory threshold test (BuOT) obtained from bilateral nasal cavities; serum total immunoglobulin E (IgE) level; and the presence of peripheral eosinophilia (PE, \> 500/mcl) in blood samples.

Safety goal of the study was evaluated by the examination of the adverse event reports and the number of patients who experienced adverse events.

Statistical analysis: The normality of the continuous variables was evaluated by the Shapiro Wilk test. Comparison of age was performed using one-way analysis of variance (ANOVA). Repeated measurements in three groups were analyzed using repeated measures ANOVA for 3×3 model with a within and a between-subjects factor. The results were assessed with a 95% confidence interval and at the p\<0.05 significance level.

A Randomized, Controlled, Triple Armed, Parallel, Open-label Phase 2 Clinical Trial

Comparison of Methylprednisolone or Methotrexate in the Maintenance Treatment of Nasal Polyposis

Comparison of Methylprednisolone or Methotrexate With Standard Treatment in the Maintenance Treatment of Medically and Surgically Treated Chronic Rhinosinusitis With Nasal Polyposis

Occurrence of polyps, edema, discharge, scar and crusting parameters were scored according to the 0-1-2 rating system.

Smell, nasal discharge, nasal obstruction, facial pressure, and headache were scored between 0 (no complaint) and 10 (most annoying)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical and Biological Effects of Anti-IgE (Omalizumab) in Patients With Bilateral Nasal Polyposis and Asthma	NCT01393340	Nasal Polyposis Asthma	Omalizumab Placebo	18 Years -	University Hospital, Ghent
Clinical and Biological Effects of Anti-IgE (Omalizumab) in Patients With Bilateral Nasal Polyposis and Asthma	NCT01393340	Nasal Polyposis Asthma	Omalizumab Placebo	18 Years -	University Hospital, Ghent
Study to Evaluate Multiple Doses in Patients With Nasal Polyposis	NCT02734849	Nasal Polyposis	AK001 low dose AK001 high dose Placebo	18 Years - 65 Years	Allakos Inc.
Nasality Evolution in a Nasal Polyposis Context : Multiparametric Evaluation : Articulatory (Imaging), Aerodynamics, Acoustics and Perception	NCT05131958	Nasal Polyposis		18 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Study to Evaluate Multiple Doses in Patients With Nasal Polyposis	NCT02734849	Nasal Polyposis	AK001 low dose AK001 high dose Placebo	18 Years - 65 Years	Allakos Inc.
Double-Blind Randomized Placebo-Controlled Trial on Clinical and Biological Effects of Oral Corticosteroids or Doxycyclin in Patients With Nasal Polyposis	NCT00480298	Nasal Polyposis	Administration ...	18 Years -	University Hospital, Ghent
Botulinum Toxin Type A Block of the Sphenopalatine Ganglion in Chronic Rhinosinusitis With Nasal Polyposis	NCT02784262	Chronic Disease Nasal Polyposis Rhinitis	botox injection...	18 Years - 70 Years	Norwegian University of Science and Technology
Comparison of Methylprednisolone or Methotrexate in the Maintenance Treatment of Nasal Polyposis	NCT04532736	Nasal Polyposis	Emthexate Prednol Mometasone Furo...	18 Years - 75 Years	Dokuz Eylul University
Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis	NCT03401229	Nasal Polyposis	Benralizumab 30... Matching placeb...	18 Years - 75 Years	AstraZeneca
Comparison of Methylprednisolone or Methotrexate in the Maintenance Treatment of Nasal Polyposis	NCT04532736	Nasal Polyposis	Emthexate Prednol Mometasone Furo...	18 Years - 75 Years	Dokuz Eylul University
Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis	NCT03401229	Nasal Polyposis	Benralizumab 30... Matching placeb...	18 Years - 75 Years	AstraZeneca
Clinical and Biological Effects of Anti-IgE (Omalizumab) in Patients With Bilateral Nasal Polyposis and Asthma	NCT01393340	Nasal Polyposis Asthma	Omalizumab Placebo	18 Years -	University Hospital, Ghent

Spots Global Cancer Trial Database for nasal polyposis